Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
  • C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
  • C07C311/52—Y being a hetero atom
  • C07C311/64—X and Y being nitrogen atoms, e.g. N-sulfonylguanidine

Definitions

• This invention relates to a method for preparingsulphonyl guanidines. More particularly it relates to a method of preparing sulphonyl guanidines by a method employing a sulphonyl guanylurea or sulphonyl dicyandiamide as an intermediate.
• sulphonyl guanidine compounds have been prepared by the reaction of various sulphonyl halides with guanidine.
• the important chemotherapeutic agent, sulphanilylguanidine was produced.
• sulphonyl guanidines, including sulphanilylguanidine can be prepared by an entirely difierent process utilizing as intermediates sulphonyl dicyandiamides or sulphonyl guanylureas.
• an aliphatic or aromatic sulphonyl dicyandiamide is subjected to hydrolysis in the presence of water or an aqueous acid solution to yield the corresponding sulphonyl guanylurea'which upon subsequent treatment with an alkaline reagent yields the corresponding guanidines.
• the production of sulphonyl guanylureas by hydrolyzing sulphonyl dicyandiamides is claimed in the copending application of Donald W. Kaiser and Jack T. Thurston, Serial No. 438,572, filed April 11, 1942.
• the aliphatic or aromatic sulphonyl guanylureas may be used as the initial starting material in my process and they may be prepared by other methods, such as for example reacting a sulfonyl halide with guanylurea, and the present invention is not necessarily dependent upon any particular method for their production.
• the aliphatic or aromatic sulphonyl dicyandiamides may be prepared in accordance with the process described in the co-pending application of Donald W. Kaiser and Jack T. Thurston, application Serial No. 438,573, filed April 11, 1942.
• EXAMPLE 1 Benzenesulphonyl guanidine A solution of 22.4 g. of benzenesulphonyl dicyandiamide in aqueous 50% ethyl ether of ethylene glycol was refluxed for three hours. After cooling slightly 4.22 g. sodium hydroxide was added and refluxing continued for fifteen. minutes. Ammonia was evolved during this time. The solution was filtered and on cooling 10.2 g. or a 51.3% yield of benzenesulphonyl guanidine, decomposing at 200-203 C was obtained. Acidification of the filtrate evolved CO2. Crystallization of the product from hot water gave glittering needles decomposing at 210- 2110 EXAMPLE. 2
• n-Butylsulphonyl guam'dine A solution of 13.3 g. of n-butylsulphonyl guanylurea in 20 g. of water which contained 2.53 g. of 95% sodium hydroxide was refluxed for thirty minutes. Ammonia began to be evolved after'five to ten minutes of heating. The solution was treated with decolorizing charcoal, filtered and allowed to cool. The colorless solid was filtered, washed with water, and air-dried. The dried solid decomposed at l5515'7 C. and weighed 8.5- g., which represents a 79% yield. Crystallization from hot water gave long, colorless needles decomposing at 157-158 C.
• the alkali insoluble material was crystallized from hot water which contained a small amount of; the ethyl ether of ethylene glycol. Beautiful needles decomposing at 208 C.-209 C. were obtained which after recrystallization decomposed at 211-212 C. The yield after deduction of the recovered starting material was 92.5%.
• EXAMPLE 4 Sulphanzlyl guanidine To a solution of 1.15 g. of 95% sodium hydroxide in 30 cc. of water was added 7.0 g. of crude sulphanilyl guanylurea. After heating to reflux a light yellow solution resulted and about seven minutes later the odor of ammonia was pronounced. Refluxing was continued for a total of thirty minutes. A little activated charcoal was added, the solution filtered, and allowed to cool. The almost solid cake or nearly colorless crystals was broken up, the solid filtered, washed with water, and allowed to dry. The crude product weighed 4.4 g. which represented a yield of 75.5%, and the material decomposed at 1'71-1'74 C. Recrystallization from hot water gave beautiful colorless plates which decomposed at 185-186 C.
• EXAMPLE 6 Benzeneswlphonyl guomidine To 24.2 g. of benzenesulphonyl guanylurea was added 8.0 g. of anhydrous sodium carbonate, 500 g. of water. The mixture was refluxed for two hours, during which time ammonia was slowly evolved. Activated charcoal was added to the slightly turbid solution and after filtration, colorless plates separated. The product was collected on a filter, washed with a small quantity of Water and dried, and a 90.5% yield of benzenesulphonyl guanidine was obtained. The product decomposed at 204-206 C. and gave no depression when fused with an authentic sample of benzenesulphonyl guanidine.
• the specific sulphonyl dicyandiamides employed as starting materials may be replaced by other sulphonyl dicyandiamides including the primary aliphatic sulphonyl dicyandiamide, ethylsulphonyl dicyandiamide, hexylsulphonly dicyandiamide, decylsulphonyl dicyandiamide, dodecylsulphonyl dicyandiamide, hexadecylsulphonyl dicyandiamide, octadecylsulphonyl dicyandiamide, 2-ethylhexy1- sulphonyl dicyandiamide, etc.; the secondary aliphatic sulphonyl dicyandiamides, isopropylsulphonyl dicyandiamide, a secondary butylsulphonyl dicyandiamide, secondary amyls
• aromatic sulphonyl dicyandiamides may be included those such as p-toluenesulphonyl dicyandiamide, p-carboxybenzenesulphonyl dicyandiamide, m-nitrobenzenesulphonyl dicyandiamide, o-brombenzenesulphonyl dicyandiamide, p-methoxybenzenesulphonyl dicyandiamide, a-naphthalenesulphonyl dicyandiamide, ,B-naphthalenesulphonyl dicyandiamide, a 5 sulphonaphthalenesulphonyl dicyandiamide, etc.
• the sulphonyl guanylureas employed in the specific examples may be replaced by other sulphonyl guanylureas including the primary aliphatic sulphonyl guanylureas, ethylsulphonyl guanylurea, hexylsulphonyl guanylurea, decylsulphonyl guanylurea, dodecylsulphonyl guanylurea, hexadecylsulphonyl guanylurea, octadecylsulphonyl guanylurea, 2 ethylhexylsulphonyl guanylurea, etc.; the secondary aliphatic sulphonyl guanylureas, isopropylsulphonyl guanylurea, secondary butylsulphonyl guanylurea, secondary amylsulphony
• aromatic sulphonyl guanylureas may be included those such as p-toluenesulphonyl guanylurea, p-carboxybenzenesulphonyl guanylurea, m-nitrobenzenesulphonylguanylurea, o brombenzenesulphonyl guanylurea, p-methoxybenzenesulphonyl guanylurea, (Jr-naphthalene sulphonyl guanylurea, p-naphthalenesulphonyl guanylurea, sulphonaphthalenesulphonyl guanylurea, etc.
• the specific alkaline reagents employed in the examples may be replaced by other suitable basic reacting substances.
• any basic substance which is more basic in reaction than guanylurea may be used in'my process for converting sulphonyl guanylureas to the corresponding sulphonyl guanidines.
• the basic substances that can be employed include those such as ammonia bases, as for example ammonia, hydroxylamines, hydrazines, guanidines, aliphatic, hydroaromatic or aromatic primary or secondary amines or polyamines.
• bases are ammonia, methyl, ethyl, propyl, butyl, amyl, decyl, dodecyl, octadecyl and cyclohexyl amines, aniline, mono-methyl, -ethyl, -propyl or -butyl anilines, hydroxylamine, N- and O-alkyl, -cycloalkyl or -aryl hydroxylamines, hydrazine and N-alkyl, cycloalkyl or aryl hydrazines, di-ethylene triamine, tri-ethylene tetramine and similar polyamines.
• the organic bases of the quaternary ammonium type are also satisfactory and include those such as tetramethylammonium hydroxide, tetraethylammonium hydroxide, benzyltrimethylammonium hydroxide, methallyltriethylammonium hydroxide, allyldimethylphenylammonium hydroxide, benzyldiethylphenylammonium hydroxide, isopropyl-triallylammonium hydroxide and the like.
• alkali metal and alkaline earth metal bicarbonates, carbonates, and hydroxides may be included.
• the quantities of alkaline reagents may be varied considerably from those illustrated and the conditions of carrying out the reactions may also be varied.
• approximately molecular equivalents of the basic substances were employed. It is not necessary that such large amounts be used and satisfactory results can be obtained using .5 molecular quantities, .1 molecular quantities, or other smaller molecular quantities.
• the process of producing sulphonyl guanidines which comprises subjecting a substance of the group consisting of aliphatic sulphonyl guanylureas and aromatic sulphonyl guanylureas to a heat treatment in the presence of water and a basic substance.
• the process of producing sulphonyl guanidines which comprises subjecting a substance of the group consisting of aliphatic sulphonyl guanylureas and aromatic sulphonyl guanylureas to a heat treatment in the presence of an aqueous solution of an inorganic base.
• the process of producing sulphonyl guanidines which comprises subjecting a substance of the group consisting of aliphatic sulphonyl guanylureas and aromatic sulphonyl guanylureas to a heat treatment in the presence of an aqueous solution of an ammonia base.
• a process of producing aliphatic sulphonyl guanidines which comprises subjecting an aliphatic sulphonyl guanylurea to a heat treatment in the presence of Water and a basic substance.
• a process of producing aliphatic sulphonyl guanidines which comprises subjecting an aliphatic sulphonyl guanylurea to a heat treatment presence of an aqueous alkali metal base.

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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Cited By (2)

• 1942
  • 1942-04-11 US US438571A patent/US2359363A/en not_active Expired - Lifetime
• 1946
  • 1946-11-23 ES ES0175833A patent/ES175833A1/es not_active Expired

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